The synthesis, processing and assembly of viral RNA and proteins will be studied in vivo and in vitro in order to (i) discover the pathway of picornavirus morphogenesis, and (ii) duplicate this pathway in vitro. In addition, a messenger RNA (mRNA)-dependent rabbit reticulocyte lysate (MDL) programmed with purified poliovirus RNA will be used so that incubation conditions can be devised to promote the synthesis and assembly of viral morphogenetic intermediates de novo from polypeptides synthesized in vitro. The achievement of these goals will lead to an understanding of the morphogenesis of picornaviruses in particular and that of other non-enveloped viruses in general. The capability of synthesizing functional viral morphogenetic intermediates (i.e., viral capsids) in vitro may eventually permit: (i) the selective encapsidation of modified viral or cellular nucleic acids for delivery to specific cells possessing receptors for such capsids, and (ii) the morphogenetic engineering of avirulent or attenuated virus strains for disease prophylaxis.